Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Medical Oncology Fellowship, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Nat Commun. 2021 Dec 6;12(1):7081. doi: 10.1038/s41467-021-27341-1.
Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors.
组织学在肺癌患者的治疗决策中起着至关重要的作用。然而，肺癌组织学的分子决定因素在很大程度上是未知的。我们对 9 名混合组织学肺癌患者的 19 个微切割肿瘤区域进行了全外显子测序和微阵列分析。在同一肿瘤的不同组织学成分之间，点突变的中位数有 68.9%是共享的，拷贝数异常的中位数有 83%是共享的。此外，肿瘤内的不同组织学成分表现出相似的亚克隆结构。另一方面，转录组分析揭示了来自不同患者的相同组织学亚型之间的共享途径，这得到了来自 141 个细胞系和 343 个不同组织学亚型的肺癌转录组数据的分析的支持。这些来自相同遗传背景和暴露史的混合组织学亚型的数据支持这样一种观点，即肺癌细胞的组织学命运与转录组特征相关，而不是与大多数肿瘤中的基因组特征相关。
